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For further information, see CMDT Part 35-04: Malaria

Key Features

Essentials of Diagnosis

  • Exposure to anopheline mosquitoes in a malaria-endemic area

  • Intermittent attacks of chills, fever, and sweating

  • Headache, myalgia, vomiting, splenomegaly; anemia, thrombocytopenia

  • Intraerythrocytic parasites identified in thick or thin blood smears or positive rapid diagnostic tests

  • Complications of falciparum malaria, including

    • Cerebral malaria

    • Severe anemia

    • Hypotension

    • Noncardiogenic pulmonary edema

    • Acute kidney injury

    • Hypoglycemia

    • Acidosis

    • Hemolysis

General Considerations

  • Four species of the genus Plasmodium are responsible for human malaria

    • P vivax

    • P malariae

    • P ovale

    • P falciparum

  • Mode of transmission

    • Bite of infected female anopheline mosquitoes

    • Can be transmitted congenitally and by blood transfusion (uncommon)

  • P falciparum is responsible for nearly all severe disease

  • P vivax seldom causes severe disease

  • P ovale and P malariae generally do not cause severe illness

  • Plasmodium knowlesi

    • A parasite of macaque monkeys

    • Causes illnesses in humans, including some severe disease, in Southeast Asia

  • For all plasmodial species, parasites may recrudesce following initial clinical improvement after suboptimal therapy

  • Disease and response to therapy are dramatically affected by immune status


  • Causes hundreds of millions of cases and hundreds of thousands of deaths each year

  • Disease is endemic in most of the tropics, including

    • Central and South America

    • Africa

    • The Middle East

    • The Indian subcontinent

    • Southeast Asia

    • Oceania

  • Transmission, morbidity, and mortality are greatest in Africa

  • Disease also common in travelers from nonendemic areas

  • Groups at particular risk for severe malaria

    • Children

    • Pregnant women

    • HIV-infected persons

    • Nonimmune travelers

Clinical Findings

Symptoms and Signs


  • Typically begins with a prodrome of headache and fatigue, followed by fever (usually irregular)

  • Without therapy, however, fevers may become regular, especially with non-falciparum disease

    • 48-hour cycles (for P vivax and P ovale)

    • 72-hour cycles (for P malariae)

  • Headache, malaise

  • Myalgias, arthralgias

  • Cough

  • Chest pain, abdominal pain

  • Anorexia, nausea, vomiting, and diarrhea

  • Seizures may represent simple febrile convulsions or evidence of severe neurologic disease

  • Physical findings may be absent or include signs of

    • Anemia

    • Jaundice

    • Splenomegaly

    • Mild hepatomegaly


  • Characterized by signs of severe illness, organ dysfunction, or a high parasite load (peripheral parasitemia > 5% or > 200,000 parasites/mcL)

  • Principally a result of P falciparum infection

  • Can include dysfunction of any system, including

    • Neurologic abnormalities progressing to alterations in consciousness, repeated seizures, and coma (cerebral malaria)

    • Severe anemia

    • Hypotension and shock

    • Noncardiogenic pulmonary edema and the acute respiratory distress syndrome

    • Acute kidney injury (due to acute tubular necrosis or, less commonly, severe hemolysis)

    • Hypoglycemia

    • Acidosis

    • Hemolysis with jaundice

    • Hepatic dysfunction

    • Retinal hemorrhages and other fundoscopic abnormalities

    • Bleeding abnormalities, including disseminated intravascular coagulation

    • Secondary bacterial infections, including pneumonia and Salmonella bacteremia



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